http://bdtd.famerp.br/handle/tede/3 2025-12-16T21:10:18Z http://bdtd.famerp.br/handle/tede/925 Título: Ocorrência de bactérias Staphylococcus spp. Meticilina-Resistentes (MRS) em animais da região de São José do Rio Preto, SP Autor: Delmaschio, Isabela Belei Primeiro orientador: Brandão, Cinara de Cássia Abstract: Introduction: Bacterial resistance is aggravated by inappropriate use of antibiotics, which amplifies the spread of resistance genes beyond disease-causing microorganisms, which ends up severely limiting the available treatment options, exposing public health risks. Staphylococci are widely distributed and are adapted to survive both in the environment and in the microbiome of humans and animals. These bacteria are responsible for a variety of infections in animals. The manifestation of Staphylococcus varies according to several interacting factors, including host immunity and resistance to antibiotics. Objectives: To investigate the occurrence of methicillin-resistant Staphylococcus (MRS) in animals treated at veterinary clinics, to identify among the Staphylococcus the most common groups in animal infections and to examine the phenotypic characteristics of resistance of the isolates to the antimicrobials evaluated in the antibiogram test. Material and Methods: The research used secondary data from culture reports and antibiograms of biological samples from animals treated at veterinary clinics in São José do Rio Preto, SP and region. It was a retrospective documentary research, with a mainly quantitative approach. Descriptive statistical analysis was performed based on calculations of measures of central tendency, dispersion and frequency counts. Results: Only the reports that indicated the presence of MRS were considered, totaling 118 cases, of which 94 were dogs (79.7%), 18 cats (15.3%), one bird (0.8%), two cattle (1. 7%), two horses (1.7%) and one lagomorph (0.8%). Of the total MRS isolates analyzed, it was observed that 73 (61.9%) were coagulase-negative, followed by 25 (21.2%) of S.aureus and 20 (16.9%) of other coagulase-positive species. The largest observations were in the auditory canal, representing 28.8% of the biological samples. Conclusions. This is the first study of MRS in animals in the region of São José do Rio Preto, SP. The bacteria examined in the study exhibited resistance to β-lactams, as well as other drug classes such as macrolides, clindamycin and quinolones. Constant monitoring of bacterial resistance is crucial to understanding resistance patterns and preventing public health risks Instituição: Faculdade de Medicina de São José do Rio Preto Tipo do documento: Tese 2023-09-22T00:00:00Z http://bdtd.famerp.br/handle/tede/924 Título: Ocorrência de enterobactérias produtoras de B-lactamases de Espectro Estendido (ESBL) em animais da região de São José do Rio Preto, SP Autor: Sanches, Leonardo Primeiro orientador: Brandão, Cinara de Cássia Abstract: Introduction: The most important mechanism of resistance to β-lactam antibiotics among Gram-negative enterobacteria are β-lactamases. Among them, extended-spectrum β-lactamases (ESBL), which are enzymes that hydrolyze the β-lactam ring, however, differ by the extent of their effectiveness and by inactivating a large part of third and fourth generation cephalosporins. The indiscriminate use of antibiotics favors the occurrence and dissemination of these enterobacteria in animals, which is a cause for great concern, as in addition to increasing morbidity and mortality, it implies, above all, increasingly challenging, restricted, and costly therapeutic options. Objectives: To investigate the presence of ESBL-producing enterobacteria in different animal species treated in veterinary clinics in the region of São José do Rio Preto, São Paulo, Brazil, and in biological samples sent to a clinical analysis laboratory from January 2019 to June 2022, as well as evaluating the bacterial resistance profile of the isolated strains to different antibiotics. Material and methods: A retrospective, cross-sectional and descriptive study was carried out using a predominantly quantitative approach. 105 culture and antibiogram reports of biological samples positive for the presence of ESBL-producing bacteria were evaluated, which were obtained from animals treated in veterinary clinics in the northwest of São Paulo. Results: Samples were identified with strains of Escherichia coli (35.2%), Klebsiella spp. (56.2%) and Proteus mirabilis (8.6%) producing ESBL. Only E. coli was isolated in samples from all animal species evaluated (dog, cat, horse, donkey, bird, bovine and swine). It was possible to identify these enterobacteria in different biological samples, with 63.8% being present in urine. The isolated strains showed resistance to different antibiotics evaluated, as well as high sensitivity to carbapenems. Conclusions: All animal species evaluated in these studies are susceptible to these ESBL-producing enterobacteria, however the occurrence was higher in dogs and cats. The predominant ESBL-producing bacteria was Klebsiella spp. and the one with the lowest occurrence was P. mirabilis. Enterobacteria were mostly identified in urine samples. The isolated strains showed remarkable resistance to β-lactam antibiotics and fluoroquinolones, and were 100% sensitive to imipenem Instituição: Faculdade de Medicina de São José do Rio Preto Tipo do documento: Tese 2023-09-29T00:00:00Z http://bdtd.famerp.br/handle/tede/923 Título: Variações na expressão fenotípica dos antígenos do sistema ABO Autor: Miola, Marcos Paulo Primeiro orientador: Mattos, Luiz Carlos de Abstract: Introduction: The ABO gene is considerably polymorphic, with more than 200 alleles that account for the expression of glycosyltransferases (GTs) that synthesize A and B antigens. These allelic variants may affect the specificity and/or activity of GTs, resulting in antigenic variations. In addition, the composition and expression of A and B antigens are also associated with enzymatic regulation factors, such as type and availability of precursors, degree of branching of their chains, types of glycoconjugates, glycoproteins or glycosphingolipids, as well as transcriptional and/or translational factors. Although antigenic variations are attributed to several known factors, these cannot always be identified or are insufficient to support a population pattern. Objective: The general objective of this study was to identify the causes of antigenic variations of the ABO blood group system in cases with unexpected phenotypic results. Material and Method: Samples of blood donors, healthy individuals, and patients who presented alterations in ABO phenotyping in routine tests were analyzed. ABO phenotyping was performed in a tube and gel column, with reagents from different clones. Red blood cells suspected of presenting weak A or B antigens were tested against a panel of anti-A or anti-B monoclonal antisera (titers 128 to 2048), respectively. Anti-A,B antiserum (titers 64 to 2048) was also used, except in cases with AB phenotype. The cases that presented mixed field (MF) with the different titers of antisera were evaluated by a technique of separation of red blood cells from MF for phenotyping of the two populations. They were also evaluated by PCR-RFLP and sequencing of the ABO and FUT2 genes. Results: All cases with weak A or B antigens, detected in direct ABO phenotyping, presented divergent results between methods and/or antisera, from non-reactive to reactive, with varying intensities (w to 4+) or in MF. The results obtained with monoclonal antisera of higher titers favored both the detection of antigens as well as the increase in the intensity of the agglutination reaction. The technique of separating the reactive from the non-reactive red blood cells of the MF allowed the phenotypic characterization of the two populations present in the case of hematopoietic mosaicism. Molecular analyses of the ABO gene by PCR-RFLP allowed the detection of the c.261delG mutation and the characterization of the O allele. The careful analysis of electropherograms obtained with sequencing favored the identification of mutations present in the ABO gene. Conclusions: Monoclonal antisera with higher titers favored the detection of weakly expressed A or B antigens in the red blood cells, as well as eliminating reactions of MF resulting from weak A or B phenotypes. In addition, anti-A,B antiserum presented better resolution when compared to anti-A antiserum of the same title. The technique of separating red blood cells from the MF, although simple, proved efficient in resolving cases of mosaicism, containing populations of red blood cells with distinct ABO phenotypes. The molecular analyses have corroborated the interpretation of the results achieved. Instituição: Faculdade de Medicina de São José do Rio Preto Tipo do documento: Tese 2023-05-05T00:00:00Z http://bdtd.famerp.br/handle/tede/922 Título: Investigação dos mecanismos moleculares associados à adesão celular, inflamação e crescimento tumoral através da expressão proteica e gênica Autor: Pirozzi, Flavio Fontes Primeiro orientador: Zuccari, Débora Aparecida Pires de Campos Abstract: Introduction: Obesity is an important risk factor for breast cancer (BC). Patients with this neoplasm and obesity have a worse prognostic factor with higher rates of metastasis, increased resistance to conventional treatments and lower survival rates. A better understanding of the role of obesity, genetic alterations and its molecular pathways is extremely important for the prevention and more individualized treatment of BC in overweight women. E-cadherin, synthesized from the CDH7 gene (gene APC/C activator protein cadherin-1) and Vimentin are proteins involved in cell adhesion and are important in the progression and risk of metastasis of BC. Both VEGF (vascular endothelial growth factor) and AKT (protein kinase B) play important roles in progression and response to treatment while interleukins (IL), especially IL-17B and IL-8, are associated with inflammatory processes and cancer. Objectives: To evaluate the role of genetic alterations and inflammatory molecular pathways of obesity in BC by gene expression (RT-PCR) and protein expression (IHC). Casuistry and Methods: We selected patients according to body mass index (BMI) - with obesity those with BMI > 30 Kg/m? and without obesity those with BMI < 30 kg/m? - and the result of the pathology (invasive ductal carcinoma or benign) and the patients were divided into four groups: group 1 (CM with obesity), group 2 (control with obesity), group 3 (CM without obesity) and group 4 (control without obesity) for analysis of gene expression of CDH1, VIM, IL17B and IL8. Among patients with BC, we selected patients with obesity (group 1a) and without obesity (group 3a) for analysis of Ecadherin, Vimentin, VEGF and AKT protein expression. Results: In the evaluation of the RT-PCR results, in the comparison between groups 1 and 3, we found no significant difference in the expression of genes CDH1 (95% CI -2.228 to 0.8815, p = 0.3771), VIM (95% CI -1.460 to 0.906, p = 0.6266), IL17B (95% CI -2.640 to 5.329, p = 0.5005) and IL8 (95% CI - 2.625 to 2.086, p = 0.8195). In the evaluation of the IHC results, in the comparison between groups 1a and 3a, we found lower protein expression of E-cadherin (95% Cl from 13.08 to 30.51, p < 0.0001) and higher protein expression of Vimentin ( 95% CI -45.46 to -28.40, p < 0.0001), VEGF (95% CI -45.00 to -27.00, p < 0.0001) and AKT (95% CI - -37.72 to -18.89, p < 0.001) in patients with obesity. Conclusions: The lower expression of E-cadherin and the higher expression of Vimentin, VEGF and AKT in patients with BC and obesity indicate that obesity not only increases the risk of developing BC, but also worsens the prognosis of the disease, increases the risk of proliferation and tumor invasion. Although we found no significant difference in gene expression between groups, we observed individual variations that highlight the heterogeneity of obesity Instituição: Faculdade de Medicina de São José do Rio Preto Tipo do documento: Tese 2023-08-01T00:00:00Z